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Infection and Immunity, October 2000, p. 5816-5823, Vol. 68, No. 10
Departments of Clinical
Immunology,1 Clinical
Bacteriology,4 and Organic
Chemistry,3 University of
Göteborg, Göteborg, Sweden, and Institute of
Biochemistry, Bucharest, Romania2
Received 21 April 2000/Returned for modification 23 May
2000/Accepted 13 July 2000
Lactoferrin (LF) is a multifunctional immunoregulatory protein that
has been associated with host defense at mucosal surfaces through its
antibacterial properties. The antibacterial and anti-inflammatory properties of LF were further explored with an animal model of experimental urinary tract infection. Bovine LF (bLF), human LF (hLF), and synthetic peptide sequences based on the antibacterial region of hLF (amino acid residues 16 to 40 [HLD1] and 18 to 40 [HLD2]) were given orally to female mice 30 min after the
instillation of 108 Escherichia coli bacteria
into the urinary bladder. The control groups received
phosphate-buffered saline or water. C3H/Tif mice were treated with hLF
or bLF, and C3H/HeN mice were treated with bLF only. The numbers
of bacteria in the kidneys and bladder of C3H/Tif and C3H/HeN mice were
significantly reduced 24 h later by the LF treatments compared to
the findings for the control group. The hLF-treated group showed
the strongest reduction compared with the
vehicle-treated-group (P values were 0.009 and 0.0001 for
the kidneys and bladder, respectively). The urinary leukocyte response
was diminished in the hLF-treated group. The hLF treatment also significantly reduced the urinary interleukin-6 (IL-6) levels at
2 h and the systemic IL-6 levels at 24 h after infection
(P values were 0.04 and < 0.002, respectively). In
the bLF-treated animals, no such strong
anti-inflammatory effects were obtained. In another series of
experiments, C3H/Tif mice perorally treated with HLD1 or HLD2
also showed reduced numbers of bacteria in the kidneys compared with
the vehicle-treated mice, although the results were significantly
different only for HLD2 (P < 0.01). Analysis of urine
from hLF-fed C3H/Tif mice showed that hLF was excreted into the
urinary tract at 2 h after feeding. Testing of the in vitro
bactericidal activity of LF (1 mg/ml) or the peptides (0.1 mg/ml) in
mouse urine against the E. coli bacteria revealed
moderate killing only by HLD2. In conclusion, these results demonstrate for the first time that oral administration of hLF or
peptides thereof is effective in reducing infection and inflammation at a remote site, the urinary tract, possibly through transfer of hLF or
its peptides to the site of infection via renal secretion. The
antibacterial mechanism is suggested to involve bactericidal capacities
of LF, fragments thereof, or its peptides.
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Human Lactoferrin and Peptides Derived from a Surface-Exposed
Helical Region Reduce Experimental Escherichia coli
Urinary Tract Infection in Mice

*
Corresponding author. Mailing address: Department of
Clinical Bacteriology, University of Göteborg, Guldhedsgatan 10, S-41346 Göteborg, Sweden. Phone: 46 31 3424728. Fax: 46 31 3424975. E-mail: inger.mattsby-baltzer{at}microbio.gu.se.
Deceased.
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